{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:01:28Z","timestamp":1787752888977,"version":"build-2784847793"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Med."],"abstract":"<jats:p>\n                    Relapse following anti-CD19 chimeric antigen receptor (CAR) T cell therapy remains a concern in the treatment of refractory B-cell malignancies. Although the CD19\n                    <jats:bold>\u0394<\/jats:bold>\n                    exon2 splice variant has been linked to treatment failure, reliable pre-treatment biomarkers for relapse risk are lacking. Here, we analyzed RNA-sequencing data from a small publicly available cohort of four anti-CD19 CAR-T-treated B-cell acute lymphoblastic leukemia patients, including one responder, one non-responder, and two who relapsed after initial response. We quantified the percent spliced in (PSI) of CD19 exon 2, as a proxy for CD19\n                    <jats:bold>\u0394<\/jats:bold>\n                    exon2 abundance before and after treatment. The patient with the lowest pre-treatment exon 2 PSI (i.e., highest estimated abundance of CD19\n                    <jats:bold>\u0394<\/jats:bold>\n                    exon2) experienced the earliest relapse, whereas the complete responder showed no detectable exon 2 skipping. In silico protein structure modeling indicated reduced structural stability of the FMC63 epitope region in the CD19\n                    <jats:bold>\u0394<\/jats:bold>\n                    exon2 variant, supporting a potential mechanistic link between exon 2 exclusion and antigen escape. Analysis of larger RNA-sequencing datasets from CAR-T treatment-na\u00efve B-cell malignancies and healthy tissues revealed low-level exon 2 skipping in some individuals across both malignant and normal B cells. These findings suggest that CD19 exon 2 skipping may correlate with relapse after CAR-T therapy, and its presence in treatment-na\u00efve individuals highlights its potential for evaluation as an RNA- or qPCR-based biomarker in future studies.\n                  <\/jats:p>","DOI":"10.3389\/fmmed.2026.1763390","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T22:10:23Z","timestamp":1770847823000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["CD19 exon 2 skipping is a potential prognostic correlate of anti-CD19 CAR-T therapy relapse"],"prefix":"10.3389","volume":"6","author":[{"given":"S\u00f8ren Helweg","family":"Dam","sequence":"first","affiliation":[{"name":"LEO foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Moranzoni","sequence":"additional","affiliation":[{"name":"LEO foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus Haraldson","family":"H\u00f8ie","sequence":"additional","affiliation":[{"name":"Department of Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"Modvig","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Copenhagen University Hospital Rigshospitalet","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Medicine, Copenhagen University","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin A. W.","family":"Wadt","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University","place":["Copenhagen, Denmark"]},{"name":"Department of Clinical Genetics, Copenhagen University Hospital Rigshospitalet","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil","family":"Als-Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University","place":["Copenhagen, Denmark"]},{"name":"Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjeld","family":"Schmiegelow","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Copenhagen University","place":["Copenhagen, Denmark"]},{"name":"Department of Pediatric and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristoffer","family":"Vitting-Seerup","sequence":"additional","affiliation":[{"name":"Department of Health Technology, Technical University of Denmark","place":["Kongens Lyngby, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike Bogetofte","family":"Barnkob","sequence":"additional","affiliation":[{"name":"Centre for Cellular Immunotherapy of Haematological Cancer Odense (CITCO), Department of Clinical Immunology, Odense University Hospital, University of Southern Denmark","place":["Odense, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars R\u00f8nn","family":"Olsen","sequence":"additional","affiliation":[{"name":"LEO foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen","place":["Copenhagen, Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet Lond. 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